Humane Toxome Project

Mapping the Human Toxome

The project will comprehensively map pathways of endocrine
disruption (ED), representing a first step towards mapping the human toxome.
The area of ED is especially suited to pioneer this approach for several
reasons: First, several large-scale testing programs, whose results can be
leveraged for this project, are already under way. Second, these testing
programs have led to the prioritization of cellular assays and reference
compounds (by EPA, NIEHS and the Interagency Coordinating Committee on the
Validation of Alternative Methods (ICCVAM)) on the national level and OECD
(Organisation for Economic Co-operation and Development) on the international
level that will be used in the project. Finally, the physiological pathways of
the endocrine system are relatively well understood, making Pathways of
Toxicity (PoT) identification simpler for ED than for other potential target
organs. The central goal of this project is to define, experimentally verify
and systematically annotate ED PoT, as a proof of concept of mapping PoT by
systems toxicology. Beyond that, this project will develop a common,
community-accessible framework and databases that will enable the toxicology
community at large to comprehensively and cooperatively map the human toxome
using integrated testing strategies that combine “omics” data with
computational models. To that end, we will achieve the following specific aims:

Use complementary “omics” approaches
(transcriptomics, metabolomics), to map and annotate PoT for a defined set
of endocrine disruptors.

Complete the development of software and
visualization tools to enable the integration, analysis and visualization
of data across multiple omics hardware platforms.

Identify PoT and develop a consensus-driven
process for pathway annotation, validation, sharing; establishment of the
public database on PoT.

Validate PoT and extend the PoT concept to
additional toxicants.

Principal investigator:Thomas Hartung, MD PhDProfessor of Toxicology (Chair for Evidence-based Toxicology),
Pharmacology, Molecular Microbiology and Immunology at Johns Hopkins Bloomberg
School of Public Health, Baltimore, and University of Konstanz, GermanyCenters
for Alternatives to Animal Testing (CAAT) at Johns Hopkins and University of
Konstanz, GermanyJohns
Hopkins University, Bloomberg School of Public Health, Baltimore, MD